TIM-3 Expression on Dendritic Cells in Colorectal Cancer
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Updated: Jun 5, 2026
Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
Published on: May 21, 2012
Mei Sakuma1, Masanori Katagata1, Hirokazu Okayama1
1Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima 960-1295, Japan.
Abstract:
TIM-3 was originally identified as a negative regulator of helper T cells and is expressed on dendritic cells (DCs). Since the inhibition of TIM-3 on DCs has been suggested to enhance T cell-mediated anti-tumor immunity, we examined its expression on DCs within the tumor microenvironment (TME) in colorectal cancer (CRC) using transcriptomic data from a public database (n = 592) and immunohistochemical evaluations from our cohorts of CRC (n = 115). The expression of TIM-3 on DCs in vitro was examined by flow cytometry, while the expression of its related molecules, cGAS and STING, on immature and mature DCs was assessed by Western blotting. The expression of HAVCR2 (TIM-3) was strongly associated with the infiltration of DCs within the TME of CRC. Immunohistochemical staining of clinical tissue samples revealed that tumor-infiltrating DCs expressed TIM-3; however, their number at the tumor-invasive front significantly decreased with stage progression. TIM-3 expression was higher on immature DCs than on mature DCs from several different donors (n = 6). Western blot analyses showed that the expression of STING was higher on mature DCs than on immature DCs, which was opposite to that of TIM-3. We demonstrated that TIM-3 was highly expressed on tumor-infiltrating DCs of CRC and that its expression was higher on immature DCs than on mature DCs.
Insights
Tumor-infiltrating dendritic cells (DCs) in colorectal cancer express TIM-3, particularly immature DCs. TIM-3 expression on DCs decreases with advancing cancer stage, suggesting a role in anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a known regulator of T cells and is expressed on dendritic cells (DCs).
- Inhibiting TIM-3 on DCs may enhance T cell-mediated anti-tumor immunity.
- Understanding TIM-3 expression on DCs within the tumor microenvironment (TME) is crucial for colorectal cancer (CRC) research.
Purpose of the Study:
- To investigate the expression of TIM-3 on DCs within the TME of colorectal cancer (CRC).
- To analyze the association between TIM-3 expression and DC infiltration in CRC.
- To compare TIM-3 expression levels on immature versus mature DCs and its relation to STING expression.
Main Methods:
- Analysis of transcriptomic data from a public database (n=592) and immunohistochemical evaluation of CRC patient cohorts (n=115).
- Flow cytometry to examine TIM-3 expression on DCs in vitro.
- Western blotting to assess the expression of TIM-3, cGAS, and STING on immature and mature DCs.
Main Results:
- TIM-3 (HAVCR2) expression strongly correlated with DC infiltration in the CRC TME.
- Immunohistochemistry confirmed TIM-3 expression on tumor-infiltrating DCs, with decreased numbers at the invasive front in advanced stages.
- TIM-3 expression was higher on immature DCs compared to mature DCs, inversely related to STING expression.
Conclusions:
- TIM-3 is significantly expressed on tumor-infiltrating DCs in colorectal cancer.
- TIM-3 expression is higher on immature DCs than mature DCs.
- The inverse relationship between TIM-3 and STING expression on DCs warrants further investigation in the context of CRC immunity.
